新規末梢循環癌細胞検出法を応用した膵癌幹細胞の治療抵抗性機序解明とその打破

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25462129
• Research Institution: Department of Clinical Research, National Hospital Organization Kure Medical Center
• Principal Investigator: 種村 匡弘 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (30379250)
• Co-Investigator(Kenkyū-buntansha): 三善 英知 大阪大学, 医学(系)研究科(研究院), 教授 (20322183) ; 江口 英利 大阪大学, 医学(系)研究科(研究院), 准教授 (90542118)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 膵癌 / 循環癌細胞 / 癌幹細胞 / 糖鎖 / 創薬 / テロメスキャン

Outline of Annual Research Achievements

【背景・目的】局所進行膵癌(PK)に強度変調放射線治療(IMRT)を用いたNACRTを行っている。同患者にTelomeScan F35を用い末梢血中の遊離癌細胞(viable CTCs)検出を行い予後予測を行い、v-CTCの有無、推移の臨床的意義を解析した。【治療・対象】PKにIMRT 60Gy+GEM +S-1によるNACRTを実施、NACRT前・後、術後にv-CTC値を測定した(N群)。同時期に実施したPK surgery first症例でも術前後v-CTC値を測定(S群)。【結果】N群は男：女＝5：11、計16例、年齢中央値は69歳。[NACRT有効性]切除不能3例を除く13例でR0手術ができ(TP:PD:DP=3:7:3)、CA19-9値、PDG-PETでは治療前に比し治療後の数値が50％以上低下した症例は各々7例、6例、標本の組織学的効果でも全例Evans分類IIa以上の効果を認めた。[v-CTC推移]5例がNACRT前よりv-CTC陽性で、5例中1例はNACRT後にv-CTCは陰性化したが、残り4例でv-CTC値はNACRT後急上昇し、術後1ヵ月でもv-CTCは陽性を維持し、術後半年～1年でv-CTCは陰性化した。v-CTC上昇の4例中1例は術後8ヵ月目に肝再発し死亡した。[S群]男：女＝5：3、計8例、年齢中央値70歳。7例にR0手術を行った(PD:DP=5:2)。術前後共にv-CTCが0であった症例は4例で、1例は術前v-CTCは陰性で術後4 cellsと上昇、S-1補助療法後v-CTCは陰性化。術前v-CTC陽性は3例で、2例は術後陰性化、残り1例は術中に微小肝転移が判明し切除不能。【結語】v-CTC陽性例に対するNACRTはPKにEMTを誘発、v-CTC遊出を惹起し早期転移巣形成が示唆され、v-CTC値は良好なバイオマーカーである。

Research Products

• [Int'l Joint Research] University of Massachusetts(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: University of Massachusetts
• [Journal Article] Incidence and risk factors of postoperative delirium in elderly patients who underwent laparoscopic surgery for colorectal cancer. (2016)
  • Author(s): Tei M, Wakasugi M, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Int J Colorectal Dis. Volume: 31(1) Pages: 67-73
  • Peer Reviewed / Open Access
• [Journal Article] Single-incision laparoscopic surgery as a teaching procedure: a single-center experience of more than 2100 procedures. (2016)
  • Author(s): Wakasugi M, Tei M, Omori T, Anno K, Mikami T, Tsukada R, Koh M, Gakuhara A, Furukawa K, Suzuki Y, Masuzawa T, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Surg Today. Volume: なし Pages: Epub
  • Peer Reviewed / Open Access
• [Journal Article] Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report. (2016)
  • Author(s): Mukai Y, Wada H, Eguchi H, Yamada D, Asaoka T, Noda T, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Umeshita K, Hori Y, Morii E, Doki Y, Mori M.
  • Journal Title: Surg Case Rep. Volume: 2(1) Pages: 29
  • Peer Reviewed / Open Access
• [Journal Article] Clinico-Pathological Significance of Leucine-Rich Alpha-2-Glycoprotein-1 in Sera of Patients with Pancreatic Cancer. (2015)
  • Author(s): Furukawa K, Kawamoto K, Eguchi H, Tanemura M, Tanida T, Akita H, Hama N, Wada H, Kobayashi S, Nonaka Y, Takamatsu S, Shinzaki S, Kumada T, Satomura S, Serada S, Naka T, Mori M,Doki Y, Miyoshi E, Nagano H.
  • Journal Title: Pancreas Volume: 44(1) Pages: 93-98
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreatic cancer immunotherapy using a tumor lysate vaccine, engineered to express α-gal epitopes, targets pancreatic cancer stem cells. (2015)
  • Author(s): Tanida T, Tanemura M, Miyoshi E, Nagano H, Furukawa K, Nonaka Y, Akita H, Hama N, Wada H, Kawamoto K, Kobayashi K, Eguchi H, Mori M, Doki Y.
  • Journal Title: Int J Oncol. Volume: 46(1) Pages: 78-90
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Discovery of α-gal epitope/natural anti-Gal antibody reaction and its clinical relevance to immunotherapy for pancreatic cancer. (2015)
  • Author(s): Tanemura M, Miyoshi E, Nagano H,Taniyama K, Mori M,Doki Y.
  • Journal Title: E-Book Volume: なし Pages: In press
  • Peer Reviewed / Open Access
• [Journal Article] Liver hilar tuberculous lymphadenitis successfully diagnosed by laparoscopic lymph node biopsy. (2015)
  • Author(s): Wakasugi M, Tanemura M, Mikami T, Furukawa K, Tsujimoto M, Akamatsu H
  • Journal Title: Int J Surg Case Rep. Volume: 10 Pages: 191-194
  • Peer Reviewed / Open Access
• [Journal Article] Signet ring cell carcinoma of the ampulla of vater: Report of a case and a review of the literature. (2015)
  • Author(s): Wakasugi M, Tanemura M, Furukawa K, Murata M, Miyazaki M, Oshita M, Yoshida K, Yasuoka H, Akamatsu H.
  • Journal Title: Int J Surg Case Rep. Volume: 12 Pages: 108-111
  • Peer Reviewed / Open Access
• [Journal Article] Cancer immunotherapy for pancreatic cancer utilizing the α-gal epitope/natural anti-Gal antibody reaction (2015)
  • Author(s): Tanemura M, Miyoshi E, Nagano H, Eguchi H, Matsunami K, Yamashita Y, Taniyama K, Hatanaka N, Akamatsu H, Mori M, Doki Y.
  • Journal Title: World Journal of Gastroenterology Volume: 21(40) Pages: 11396-11410
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Single-incision totally extraperitoneal inguinal hernia repair as a teaching procedure: one center's experience of more than 300 procedures. (2015)
  • Author(s): Wakasugi M, Tei M, Anno K, Mikami T, Tsukada R, Koh M, Furukawa K, Suzuki Y, Masuzawa T, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Surg Today. Volume: なし Pages: Epub
  • Peer Reviewed / Open Access
• [Presentation] 脂肪由来幹細胞(ADSC)を応用した次世代型膵島移植療法の開発 ― 生着改善に向けた膵島移植のブレイクスルー ― (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本臨床外科学会総会
  • Place of Presentation: 福岡、博多
  • Year and Date: 2015-11-26 – 2015-11-26
• [Presentation] Significant cross-reactive responses to pancreatic cancer cells induced by tumor lysate vaccine remodeled to express α-gal epitopes and their implications for a universal cancer vaccine (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-10-10 – 2015-10-10
• [Presentation] The detection of viable human circulating tumor cells in resectable pancreatic cancer (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15 – 2015-07-15
• [Presentation] 糖鎖リモデリングによる多様性癌抗原に対応したユニバーサル膵癌ワクチン療法確立への可能性 (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本肝胆膵外科学会総会
  • Place of Presentation: 東京、台場
  • Year and Date: 2015-06-12 – 2015-06-12
• [Presentation] Viable Circulating Tumor Cells測定(v-CTC値)から見た局所進行膵癌に対する術前化学放射線療(NACRT)の功罪 ―NACRTによりv-CTCs遊出を誘導する― (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本外科学会定期学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-04-16 – 2015-04-16
• [Book] 膵島の再生医療 –膵β細胞の発生と再生をめぐる新展開– 脂肪組織由来幹細胞を応用した次世代型膵島移植の確立 (2015)
  • Author(s): 種村匡弘
  • Total Pages: 123-129
  • Publisher: 診断と治療社